The present invention relates to a new process for the preparation of corroles and to a new class of corroles. The new class of corroles includes inter alia, water-soluble corroles and chiral corroles.
The simplest corrole has the following structure: 
As shown in the above formula, corroles are slightly contracted porphyrins. Porphyrins are tetrapyrroles. They consist of four pyrrole rings (which are weakly aromatic) joined by methene bridges in a cyclic configuration, to which a variety of side chains are attached.
The metal complexes of porphyrin derivatives are involved in the most important biochemical processes, such as the binding and transportation of oxygen (the heme in myo- and hemoglobin), electron transfer (the heme in cytochromes), oxidation as part of biosynthesis and biodegradation (metabolism) of organic and inorganic compounds (heme-dependent enzymes), photosynthesis (magnesium chlorin in chlorophylls), and in Vitamin B12 (cobalamin, with a reduced cobalt corrole structure). Synthetic metal complexes of porphyrins are extensively utilized as oxidation catalysts, as well as for other catalytic transformations. Also, a numerous number of porphyrins and their metal complexes are constantly tested for biomedical purposes, most notable for treatment of cancer and AIDS.
Corroles are much less known than porphyrins and their synthesis is a very complicated matter (a) Sessler, J. L.; Weghorn, S. J. in Expanded, Contracted, and Isomeric Porphyrins, Pergamon, Oxford, 1997, pp. 1-503. b) Vogel, E. J. Heterocyc. Chem. 1996, 33, 1461. c) Licoccia, S.; Paolesse, R. Struct. Bond. 1995, 84, 71). The first corrole was reported in 1965, and although the synthetic methods were improved during the years passed, there is still no simple procedure for that purpose. In this respect, even in the single and recently reported one-pot corrole synthesis (Ohyama, K.; Funasaki, N. Tetrahedron. Lett. 1997, 38, 4113), the dipyrrolic starting material is not commercially available and is also quite unstable. Because of the severe difficulties in the preparation of corroles, their potential in the fields where porphyrins were proven to be highly efficient was never explored.
It is an object of the present invention to provide a new and simple process for the preparation of corroles, starting from relatively simple and commercially available starting materials.
It is another object of the invention to provide novel corroles, their salts, optically active enantiomers and metal complexes thereof.
The synthetic approach relies on a one-pot, solvent-free condensation of an aldehyde with a pyrrole. All starting materials are commercially available and stable at ambient conditions (temperature, air, humidity) and the reaction yields are reasonable, considering the complexity of the products.
The term xe2x80x9csolvent-freexe2x80x9d refers to a reaction carried out without any solvent but may be performed with the aid of solid material, such as chromatographic supports or metal salts.
Thus, the present invention provides a process for the preparation of corroles of the following formula I: 
wherein:
each R1 is hydrogen or is selected from straight or branched C1-C12 alkyl, aralkyl, aryl, heteroaryl, where any of these radicals may be substituted;
R2 and R3 are identical or different and each R2 and each R3 represents hydrogen or a radical selected from straight or branched C1-C12 alkyl, aralkyl, aryl, where any of these radicals may be substituted, and
R4, R5 and R6 are each hydrogen or represent identical or different radicals selected from straight or branched C1-C12 alkyl, aralkyl, aryl, acyl, alkylsulfonyl or arylsulfonyl. where any of these radicals may be substituted;
which process comprises solvent-free condensation of an aldehyde of formula II with a pyrrole of formula III 
wherein R1, R2 and R3 are as defined above, followed by dehydrogenation, to obtain a compound of formula I wherein R4, R5 and R6 are hydrogen,
and if desired converting said compound of formula I to a compound of formula I wherein at least one of R4, R5 or R6 is other than hydrogen,
and if desired converting any compound obtained into a salt or a metal complex.
Further disclosed are several new compounds of formula I, salts and metal complexes thereof. Also provided are optically pure enantiomers of these novel compounds. The metal complexes of the compounds of formula I were found to behave as very efficient catalysts in synthesis, for example in cyclopropanation or oxidation of hydrocarbons and in the alkylation of electrophilic derivatives. Some of the new corroles are easily converted into water-soluble derivatives, such feature being crucial for exploring certain potential applications.
As stated above, one object of the present invention is to provide a new process for the preparation of corroles, the main advantages of which are listed below:
1. The synthetic procedure is a one-pot synthesis.
2. All starting materials are simple and commercially available.
3. The amount of chemicals, other than those which are absolutely required as the basic building blocks of the final material, is heavily reduced compared to all other known methods.
The new corroles which were prepared by the novel process described in this invention may be described by the general formula I: 
wherein
each R1 hydrogen or is selected from straight or branched C1-C12 alkyl, aralkyl, aryl, or heteroaryl, where any of these radicals may be substituted,
R2and R3 are each hydrogen, and
R4, R5 and R6 are each hydrogen, or one of them may represent a radical selected from straight or branched C1-C12 alkyl, aralkyl, aryl, carboxyl or sulfonyl, where any of these radicals may be substituted.
The R1 group may have, for example the following meanings: 2,3,4,5,6-pentafluorophenyl; 2,6-difluorophenyl; 2,6-dichlorophenyl; 4-(2-pyridyl)-2,3,5,6-tetrafluorophenyl and 4-(N-methyl-2-pyridylium iodide)-2,3,5,6-tetrafluorophenyl. Several new corroles which were prepared by the process of the present invention are shown in the following formulae 1-9 in Scheme 1: 
Other examples of new corroles according to the present invention are chiral corroles wherein one of the protons attached to the nitrogen in the pyrrole ring is replaced by a substituent, as for example an alkyl, alkylaryl, aryl, aralkyl, carboxy, or sulfuryl group. These chiral corroles may be represented by formulae IV and V as follows: 
wherein R1 is as defined above and R has the same meanings as given for either of R4, R5 and R6 above. The structures shown in formulae IV and V represent the N(21)- and N(22)-substituted corroles, respectively. Both structures are chiral and can be resolved into enantiomers by crystallization in the presence of an enantiomerically pure acid.
The metal complexes of the corroles of formula I were found to behave as efficient catalysts. The structures of some novel metallocorroles according to the present invention are shown in Scheme 2 below: 
The following equations show potential uses of metallocorroles as catalysts in organic synthesis, for example in epoxidation or cyclopropanation reactions: 
In reaction (2) above X might be either a non chiral substituent such as for example an EtOxe2x80x94 group or a chiral substituent such as (+) or (xe2x88x92)2,10-camphorsultam.
The chiral corroles of the present invention, such as for example compounds 6-9 shown in Scheme 1 above, also exhibit catalytic effect on the addition of diethylzinc to aldehydes: 
The substituent R may be a group selected from straight or branched C1-C12 alkyl, aralkyl, aryl, or heteroaryl.
The corroles of the present invention and the derivatives thereof such as metal complexes) have unique properties which are relevant to arious applications. Potential applications are in the fields of organic dyes and inks, non linear optics (NLO), conducting material, sensors (pH, ions, oxygen, etc.), conversion of solar energy to chemical and electrical energies.
The most potential applications of the corroles of the invention and their metal complexes are derived at least partially, from the following features:
1. The color of the corroles is highly sensitive to pH changes, as the neutral form is purple-red, while both the protonated (at pH less than 2) and the deprotonated forms (at pH greater than 7) are intense-green.
2. A prerequisite for NLO and other applications which are based on molecules with a permanent dipole is the synthesis of asymmetrically substituted compounds. The advantage of the corroles in this context, is in view of the fact that their less symmetric structure (point symmetry of C2v, like water) has an intrinsic polarity.
3. Properties as for example, conductivity, photoconductivity, photoluminescence, etc. are based on strong intermolecular interactions. The preliminary results with the iron and copper complexes of the corroles show that this interaction is stronger than in porphyrins. Thus, the corrole-corrole interactions in the xcexc-oxo dimer (1)2(Fe)2O shown in Scheme 2 are much stronger than in analogous porphyrin dimers.
4. The water-soluble derivatives of corroles, such as compound 5 shown in Scheme 1, undergo pH-dependent protonation and deprotonation processes in water.